The long-term goal of the proposed project is to elucidate mechanisms underlying gender-related differences in myocardial aging. Preliminary results demonstrated differences in myocardial remodeling and in expression of SR Ca2+-ATPase between male and female F344/BN rats with advancing age. In the proposed project the following objectives will be studied: 1) : The hypothesis will be tested that with advancing age cardiac function in male F344 B/N rats decompensates to. a greater extent than in female rats, and that female hearts undergo more concentric remodeling than male hearts. In vivo cardiac function and ventricular morphology will be studied. Mechanisms underlying gender-specific adaptations will be examined by studying myocyte shortening, Ca2+-dynamics, and programmed cell death. Results from these studies will help to determine the relative importance of myocyte dysfunction vs. myocardial cell loss in myocardial aging between the two genders. 2) The hypothesis will be tested that in advanced age hearts of female F344/BN rats can better adapt to stress compared to hearts of male rats. We postulated that pressure overload causes greater decompensation, in terms of myocardial contractile function and remodeling, in aged male rats than in female rats. Myocyte size, cell shortening, Ca2+-dynamics, and apoptosis will be examined to elucidate the underlying mechanisms. The short-term goal of the proposed study is to confirm and establish that the aging F344/BN rat is a relevant and unique model for studying gender differences in myocardial aging, and to begin elucidating the underlying mechanisms. Results from the proposed studies may help identify cellular targets responsible for gender-specific adaptation of the aged heart and help facilitate development of better gender-specific strategies in diagnosis and treatment of heart failure in the elderly. The ultimate goal is to develop interventions, which may be gender specific, that may delay or reverse myocardial aging.